The work proposed for this fellowship is part of a larger project that the long term goal of exploiting virus gene products to treat human malignancy. Epstein-Barr virus,2 a human herpesvirus, is associated with several human malignancies. Herpesviruses respond well to antiviral therapy. Treatment of EBV related tumors with antiviral therapy could be possible. In this proposal, the mechanism of regulation of the EBV thymidine kinase (TK) gene will be investigated. Such knowledge may reveal a mechanism to upregulate its expression in latently infected EBV+ tumor cells by treatment with drugs that induce the proper viral and/or cellular transcription factors. This project represents necessary groundwork for testing the hypothesis that induction of EBV TK gene expression, coupled with effective antiviral treatment, may be a successful means of eradicating EBV+ tumor cells. This project will also yield basic research information on the control of gamma-herpesvirus early gene expression.